Substance release device

ABSTRACT

The invention relates to a device for releasing active agents, characterized in that at a frequency of 0.1 rad/s, it has a glass transition temperature of less than 15° C., contains at least 3% by weight of an SEPS block copolymer and contains at least one substance with a local or systematic effect which does not cause hyperaemia. The device is not foamed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase filing of and claims the benefit ofPCT/EP99/00582 filed Jan. 29, 1999.

The invention relates to a device for releasing at least one substance.One particular embodiment constitutes a backing material and, applied atleast partially thereon, a device in the form of an adhesive compositioncomprising the one or more active substances that are delivered to theskin.

Transdermal therapeutic systems (TTS) are forms of administration ofmedicaments that deliver one or more medicaments to the skin over adefined period at their location of use. A distinction is made herebetween systemic and local administration forms.

With systemic administration forms, the active substance passes throughthe skin into the bloodstream by diffusion and can act within the bodyas a whole. Local administration forms, on the other hand, act only atthe sites of application. The active substance remains in the skin or inthe underlying layers.

Strongly adhering plasters are normally coated over their entire areawith a rubber adhesive composition. The sticking of such products to theskin gives rise, following their removal, to marked skin irritations andmechanical stressing of the skin. Without auxiliary media it isimpossible to break the bond painlessly. In some cases, there areallergic reactions. Furthermore, the adhesive compositions used oftenlead to a transfer of composition onto the skin.

The use of skin-friendly adhesive compositions, such as acrylateadhesive compositions and hydrogels, is out of the question because oftheir low shear stability and tack. Improvement through aftertreatment,especially crosslinking, though possible, nevertheless gives a resultwhich is unsatisfactory overall. The proprioreceptive effect is lessthan that of systems with a rubber adhesive composition.

Other known adhesive systems based on conventional block copolymers arehowever not skin-friendly, owing to the high level of stabilizer added,or because of the high levels of cohesiveness have been found suitableto date only for industrial applications; alternatively, they cannot beformulated for strong adhesion and sticking to the skin.

The abovementioned adhesive compositions are pressure-sensitiveself-adhesive compositions which may be present in a carrier matrix forprocessing. The term carrier matrix is understood to refer to commonorganic or inorganic solvents or dispersion media.

Systems without a carrier matrix are referred to as 100% systems and arelikewise not unknown. A common mode of processing is that of the melt.Pressure-sensitive hot melt adhesive compositions of this kind have alsoalready been described in the prior art. They are based on natural orsynthetic rubbers and/or other synthetic polymers.

An advantage of the 100% systems is that they avoid an operation ofremoving the carrier matrix, i.e. the auxiliary media, thereby raisingthe productivity of processing and at the same time reducing theexpenditure on machinery and the energy costs. In addition, this reducesthe occurrence of residues of the carrier matrix, which, in turn, isbeneficial to a reduction in the allergenic potential.

Because of their high level of hardness, sticking to the skin is aproblem for such 100% systems.

It is also known to apply such self-adhesive compositions not only overthe entire area but also in the form of a pattern of dots, for exampleby screen printing (DE-C 42 37 252), in which case the dots of adhesivecan also differ in their size and/or distribution (EP-B 353 972), or byintaglio printing, in lines which interconnect in the longitudinal andtransverse directions (DE-C 43 08 649).

The advantage of the patterned application is that the adhesivematerials, given an appropriately porous backing material, are permeableto air and water vapour and, in general, are readily redetachable.

A disadvantage of these products, however, is that if the area coveredby the adhesive film, which is impermeable per se, is too large there isa correpsonding reduction in the permeability to air and water vapour;the consumption of adhesive composition rises, and, if the area coveredby the adhesive film is small, the adhesion properties deteriorate, i.e.the product is detached too readily from the substrate, especially inthe case of heavy, textile backing materials.

Numerous embodiments of active substance plasters have already beendescribed in the prior art, some of them operating in accordance withthe reservoir principle, where the active substance is delivered, forexample, by way of a membrane, in some cases also with a matrix systemor with a relatively complex multilayer structure.

It is also known that the adhesive composition of the plaster can beemployed as the matrix comprising active substance. In addition toself-adhesive compositions applied from solution, hotmelt self-adhesivecompositions have also been proposed for this purpose, as for example inEP-A 663 431, EP-A 452 034, EP-A 305 757, DE-A 43 10 012, DE-A 42 22 334and DE-C 42 24 325. The active substances listed in these documents, ifnamed at all, have been systemic ones.

Examples of active substance plasters are antimycotic and keratolyticactive substance plasters and those which aid the circulation.

However, plasters of this kind, which occasionally have to be appliedover a relatively large area, in some cases exhibit distinct mechanicalskin irritations after removal in the case of sensitive patients. Insome cases there are allergic reactions. After a prolonged period ofwear, their removal is to some extent painful.

A further disadvantage of the known thermally active plasters with anadhesive composition based on natural rubber, which is applied in theform of a solution with organic solvents to the plaster backing, is thecomparatively low rate of release of the active substance.

The abovementioned disadvantages, and more, also apply to activesubstance plasters comprising substances other than those mentioned.

For instance, WO 94/02123 describes an active substance plaster based onpressure-sensitive hotmelt adhesive compositions and comprisinglow-melting and/or readily volatile active substances in a concentrationof from 2.5 to 25% by weight. The polymers employed in that document areA-B-A triblock styrene-ethylene-butylene-styrene block copolymers whichare notable for low initial tack and low bond strength on skin.

EP 0 663 431 A2, EP 0 443 759 A3, EP 0 452 034 A2 and U.S. Pat. No.5,371,128 describe uses of pressure-sensitive hotmelt adhesives, basedon silicone, with diverse additives and in differentiated forms ofconstruction.

DE 43 10 012 A1 describes the construction of a dermal therapeuticsystem from meltable poly(meth)acrylate mixtures.

In particular, difficulties are apparent in the release of two or moreactive substances from polymer systems formed from only one type ofpolymer. Systems with two or more types of polymer, however, arecritical in terms of their compatibility.

DE 43 16 751 C1 describes a multi-chamber system for administeringactive substances.

EP 0 439 180 describes an active substance plaster for administeringtolubuterol.

EP 0 305 757 describes an active substance plaster for administeringnicotine.

EP 0 305 758 describes an active substance plaster for administeringnitroglycerine.

EP 0 305 756 describes a device for releasing substances, and thepreparation and use thereof.

DE 37 43 945 describes a device for delivering substances, and thepreparation process. In the case of the pressure-sensitive hotmeltadhesive composition described, which is based on SIS, the device is notself-adhesive. The processing ranges indicated therein lie well belowthose of hotmelt adhesive compositions and for such systems describedwould not provide sufficient anchorage of the adhesive composition.

WO 96/22083 indicates a polyisobutylene adhesive for transdermalpurposes, having a tackifier with a high glass transition point. Theadhesive is not foamed.

JP 07-196505 describes the administration of indomethacin in hotmeltpressure-sensitive adhesives. In this case, a polyethylene foam is usedas backing material.

EP 0 428 017 describes an adhesive composition based on SEBS and SEPSblock copolymers. There is no description, however, of the release ofsubstances with a local or systemic action.

U.S. Pat. No. 5,085,655 describes the use of SEPS block copolymers as acohesive sticking system, especially of nappies and panty liners. Thepossibility of releasing substances is not described.

JP 09 188 865 describes a system based on synthetic block polymers. Therelease of substances is not described.

JP 08277382 describes a system based on SEPS which is used as a hotmeltadhesive composition for nappies and sanitary towels. The release ofsubstances is not described.

JP 08209094 describes a system based on synthetic block polymers. Therelease of substances is not described.

JP 03160083 describes a system based on SEPS which is used as a hotmeltadhesive composition for nappies and sanitary towels. The release ofsubstances is not described.

The object of the invention is therefore to provide a device whichcomprises one or more active substances and which, while avoiding thedisadvantages known from the prior art, features a high level ofefficacy, i.e. a relatively high rate of release, even in the case ofdifferent combinations of active substances, and good skin compatibilitycoupled with good adhesion. In addition, the device should be able to beprepared in a technically simple and environmentally compatible manner.

This object is achieved by a device for releasing substances as is setout in the main claim. The subclaims relate to advantageous embodimentsof the devices of the invention. The invention also embraces processesfor producing such devices.

The invention accordingly provides a device for releasing activesubstances which at a frequency of 0.1 rad/s has a glass transitiontemperature of less than 15° C. and an SEPS block copolymer content ofat least 3% by weight and comprises at least one locally or systemicallyacting substance, in the preferred embodiment a variety of activesubstances. The active substance or substances are not hyperaemic;furthermore, the device should not be foamed.

SEPS here stands for styrene-ethylene-propylene-styrene, comprising ablock copolymer on the basis of polystyrene blocks (S) and blocks ofhydrogenated polyisoprene (EP) or hydrogenatedpoly(butadiene-co-isoprene) (EEP). Diblocks, triblocks and multiblocksmay be used.

In one advantageous embodiment the device has an A/B diblock fraction ofmore than 30%, preferably greater than 60%.

Preferably, the quantitative concentrations of the active substance orsubstances in the adhesive composition lie between 0.01 to [sic] about60% by weight, preferably from 0.1 to 20% by weight.

By active substances in the context of the present invention are meantchemical elements and organic and inorganic compounds which are able tomigrate from the constituents of a generic device that comprise them andso bring about a desired effect. Among the fields of use of the deviceof the invention, human and veterinary medicine are of particularimportance, and in this context a configuration of the invention inplaster form is particularly preferred.

Typical active substances—with no claim to completeness—for theproduction of plaster systems doped with active substance are, in thecontext of the present invention, as follows:

Indication: Active substance Antimycotics nafitine [sic] amorrolfine[sic] tolnaftate ciclopirox Antiseptics thymol eugenol triclosanhexachlorophen benzalkonium chloride clioquinol quinolinol undecenoicacid ethacridine chlorohexidine hexetidine dodicine iodine Nonsteroidalantirheumatics glycol salicylate flufenamic acid etofenamate ketoprofenpiroxicam indomethacin Antipruritics polidocanol isoprenaline crotamitonLocal anaesthetics benzocaine Antipsoriatics ammonium bitumasulphonateKeratolytics urea

The active substances are dispersed in the device preferably in athermal homogenizer, such as thermal mixers, thermal kneading apparatus,roll mills or screw systems, for example. The active substance can beadded to the ready-produced device. The active substance can also, forexample, be incorporated into an intermediate stage or into the initialmixture.

The device is advantageously an adhesive composition which in aparticularly preferred embodiment is a hotmelt adhesive compositionhaving an SEPS block copolymer fraction of at least 3% by weight. In onepreferred embodiment, triblock copolymers are used. For specificdevices, SEP diblock or multiblock polymers are advantageous.

The bonding properties can be adjusted depending on the field of use. Incertain cases, strongly self-adhering systems or else systems withpressure-sensitive adhesion are required. To make these adjustments,appropriate additives are added to the polymer system, such as tackifierresins, plasticizers, stabilizers and other auxiliaries.

Their softening point should be higher than 50° C., since theapplication temperature is generally at least 70° C., preferably between90 and 150° C. If desired, subsequent crosslinking by irradiation withUV or electron beams may be appropriate. This depends on the specificcomposition of the main polymer or the additives thereto.

It is particularly advantageous for further polymers to be present inthe device, these polymers preferably being based on block copolymers.Blends of block copolymers based on SEPS and SEBS, in particular, arenotable for their diverse possibilities for variation, since thetargeted reduction in the glass transition temperature of theself-adhesive composition, as a result of the selection of tackifiers,plasticizers, polymer molecule size and molecular distribution of thecomponents employed, ensures the necessary bonding with the skin in amanner appropriate to their function, even at critical sites on thehuman locomotor system.

The high shear strength of the hotmelt self-adhesive composition isachieved by the cohesive character of the polymer. The good tack resultsfrom the range of tackifiers and plasticizers employed.

For systems which adhere particularly strongly the hotmelt self-adhesivecomposition is based preferably on block copolymers, especially A-B orA-B-A block copolymers or mixtures thereof. The hard phase A isprimarily polystyrene or its derivatives and the soft phase B comprisesat least one soft phase B based on ethylene, butylene, propylene,isoprene, butadiene or mixtures thereof.

As a further preference, the polymers and the device are constructed onthe basis of diblock (A-B) and/or triblock (ABA) copolymers, with afraction of diblock copolymers of less than 80% by weight.

The chain of phase B may also include sections of other types, such asisoprene, butadiene or similar substances, for example. Polystyreneblocks may also be present in the soft phase B, in an amount of up to20% by weight. The overall proportion of styrene, however, should alwaysbe less than 35% by weight. Preference is given to styrene contents ofbetween 3% by weight and 30% by weight, since a lower styrene contentmakes the adhesive composition smoother.

The controlled blending of diblock and triblock copolymers isparticularly advantageous, preference being given to a proportion ofdiblock copolymers of less than 80% by weight.

The adhesive composition may also include auxiliaries for particularrelease, or to assist such release. Examples here are polypropyleneglycol and polyethylene glycol.

In one advantageous embodiment, the hotmelt self-adhesive compositionhaving a SEPS block copolymer proportion of at least 3% by weight hasthe composition indicated below:

from 3 to 90% by weight of block copolymers,

from 5 to 80% by weight of tackifiers, such as aliphatic hydrocarbonresins, hydrogenated terpene resins, hydrogenated hydrocarbon resins,cyclopentadiene resins, styrene-α-methylstyrene resins and low molecularmass polyisobutylenes,

less than 60% by weight of plasticizers, such as paraffin oils,aliphatic hydrocarbon oils, waxes and fatty acetates and alcoholates,

less than 15% by weight of additives,

less than 20% by weight of active substance release auxiliaries, and

less than 5% by weight of stabilizers,

less than 60% by weight of active substance or substances.

The tackifiers and plasticizers serve to establish the bondingproperties and the stability. If desired, further stabilizers and otherauxiliaries are employed.

The following polymer/tackifier combinations are given by way ofexample.

Type E1 E2 E3 SEPS (Kuraray Co.) T1 30 10 Styrene content 13% T2 20 40SEBS (Shell) T3 5 Styrene content 30% T4 5 Hydrocarbon resin 40 49 40Hydrocarbon oil 24 15 19 Antioxidant 1 1 1

Combinations of other polymer systems are obvious to the person skilledin the art.

It is possible to fill the adhesive composition with mineral fillers,fibres or hollow or solid microbeads.

The hotmelt self-adhesive composition has a softening point of more than50° C., preferably from 70 to 220° C. and, with very particularpreference, from 75 to 140° C.

The dynamic glass transition temperature of the elastomer phase of theadhesive matrix, at a frequency of 0.1 rad/s, is less than 15° C.,preferably from −3 to −30° C. and, with particular preference, from −9to −25° C.

Plasters in particular are subject to stringent requirements in terms oftheir bonding properties. For ideal application, the hotmeltself-adhesive composition should possess a high tack. There should befunctionally appropriately bond strength to the skin and to the reverseof the backing. So that there is no slipping, the hotmelt self-adhesivecomposition is also required to be of high shear strength.

The targeted reduction in the glass transition temperature of theself-adhesive composition, as a result of the selection of thetackifiers, plasticizers, polymer molecule size and moleculardistribution of the components employed, achieves the necessary bonding,appropriate to its function, with the skin and with the reverse of thebacking.

The high shear strength of the self-adhesive composition employed hereis achieved by the high cohesiveness of the block copolymer. The goodtack arises from the range of tackifiers and plasticizers that isemployed.

Product properties such as tack, glass transition temperature and shearstability can be quantified readily using a dynamomechanical frequencymeasurement. In this case, use is made of a rheometer controlled byshearing stress. The results of this measurement method give informationon the physical properties of a substance by taking into account theviscoelastic component. In this instance, at a preset temperature, thehotmelt self-adhesive composition is set in oscillation between twoplane-parallel plates with variable frequencies and low deformation(linear viscoelastic region). Via a pickup control unit, with computerresistance, the quotient (Q=tan δ) between the loss modulus (G″, viscouscomponent) and the storage modulus (G′, elastic component) is measured.

Q=tan δ=G″/G′

A high frequency is chosen for the subjective sensing of the tack and alow frequency for the shear strength.

A high numerical value denotes better tack and poorer shear stability.

The complex-dynamic glass transition point is the point of transitionfrom the amorphous to the viscoelastic region. It corresponds to themaximum of the temperature function at a predetermined frequency.

T_(g) low Conformity Tack Designation frequency low frequency/RT highfrequency/RT Self-adhesive  4 ± 2° C. tan δ = 0.08 ± 0.03 tan δ = 0.84 ±0.03 composition A Self-adhesive −9 ± 2° C. tan δ = 0.32 ± 0.03 tan δ =1.70 ± 0.03 composition B

In accordance with the invention, preference is given to hotmeltself-adhesive compositions for which the ratio of the viscous componentto the elastic component at a frequency of 100 rad/s at 25° C. isgreater than 0.7, or to hotmelt self-adhesive compositions for which theratio of the viscous component to the elastic component at a frequencyof 0.1 rad/s at 25° C. is less than 0.6, preferably between 0.35 and0.02 and, with very particular preference, between 0.3 and 0.1.

In exceptional cases, a modified use of the device can be achieved by itbeing foamed.

In this case, the devices with the active substances added to them arepreferably foamed using inert gases such as nitrogen, carbon dioxide,noble gases, hydrocarbons or air, or mixtures of these. In some cases,foaming additionally by thermal decomposition of gas-evolvingsubstances, such as azo, carbonate and hydrazide compounds, has beenfound suitable.

The degree of foaming, i.e. the gas content, should be at least about 5%by volume and can range up to about 85% by volume. In practice, levelsof from 10 to 75% by volume, preferably 50% by volume, have been foundappropriate. Operating at a relatively high temperature of approximately100° C. and with a comparatively high internal pressure produces veryopen-pored adhesive foam layers which are particularly permeable to airand water vapour.

The advantageous properties of the device include its good conformityeven on uneven surfaces, owing to the elasticity and plasticity of thefoamed device.

At the same time, the vacuoles in the foam bring about a more thanproportional increase in the transportation of the active substances, asa result of which very good release rates are achieved.

A particularly suitable process for producing the device foamed inaccordance with the invention operates by the foam mixing system. Inthis system, the thermoplastic adhesive composition is reacted with theintended gases, such as nitrogen, air or carbon dioxide, for example, invarious volume proportions (from about 10 to 80% by volume) in astator/rotor system under high pressure and at a temperature above thesoftening point (approximately 120° C.).

Whereas the gas entry pressure is greater than 100 bar, the mixingpressures between gas and thermoplastic in the system are from 40 to 100bar, preferably from 40 to 70 bar. The pressure-sensitive adhesive foamproduced in this way can subsequently pass through a line into theapplicator unit. In the applicator unit, commercially customary nozzles,extruder systems or chamber systems are used.

The interaction of the active substances with the skin is, as is known,modulated by enhancers that are mixed into the adhesive composition orintensified by the occlusive effect of adhesive composition andcovering. In contrast to this it is possible, with the use of breathabledoped coatings in conjunction with elastic and likewise breathablebacking materials, in particular for example during sporting activities,to achieve

a) a level of wear comfort which is perceived subjectively as morepleasant by the user and

b) as a result of an interaction of the skin with the environment (forexample suppression of perspiration) that is less disturbed by therelease behaviour, a more defined penetration of active substances intothe skin.

In contrast, it is also possible by virtue of the processes mentionedhere to achieve permeability of the doped plaster system from theoutside. By virtue of this property of the product, therefore, it ispossible following actual application for substances to be brought tothe contact point between doped adhesive/skin, through the backing, evenat a later time (sprinkling on of liquid, wiping, etc.). Thesesubstances might, for example, comprise an additional enhancer effect ormight initiate or attenuate the pharmaceutical action or modulate itappropriately for a favourable consumer response.

By virtue of the foaming of the device and the open pores in thecomposition which form as a result, and given the use of an inherentlyporous backing, the products coated with the device are of goodpermeability to water vapour and air. The amount of device required isconsiderably reduced without adverse effect and mode of action of thedevice properties [sic].

Foaming also generally reduces the viscosity of the device. This lowersthe melt energy, and even thermally unstable backing materials can becoated directly.

It is also advantageous, especially for use with medical products, ifthe doped composition is applied partially to the backing material, forexample by halftone printing, thermal screen printing, thermalflexographic printing or intaglio printing, because backing materialswhich have been self-adhesively treated in a continuous applied line mayin adverse circumstances induce mechanical skin irritations whenapplied.

It is also possible, furthermore, to apply the adhesive composition, forexample, by spraying, which produces a more or less irregular pattern ofapplication.

Partial application makes it possible, through controlled channels, todissipate the transepidermal water loss, and improves the removal ofsweat from the skin in vapour form, especially when the backingmaterials used are permeable to air and water vapour. By this means theskins irritations induced by an accumulation of body fluids are avoided.The dissipation channels that have been set up enable fluids to beconducted away.

Preference is given to application in the form of polygeometric domes,especially those where the ratio of diameter to height is less than 5:1.Printed application of other forms and patterns on the backing materialis also possible—for example, a printed image in the form ofalphanumeric character combinations or patterns such as matrices,stripes and zigzag lines.

The doped composition can be distributed uniformly over the backingmaterial; alternatively, it can be applied with a thickness or densitywhich varies over the area, as appropriate to the function of theproduct.

The principle of thermal screen printing consists in the use of arotating, heated, seamless, drum-shaped, perforated, cylindrical screenwhich is fed via a nozzle with the preferred composition. A speciallyshaped nozzle lip (circular- or square-section coating bar) presses thecomposition, which is fed in via a channel, through the perforation ofthe screen wall and onto the backing web that is conveyed past it. Thisbacking web is guided by means of a counterpressure roller against theexternal jacket of the heated screen drum at a rate which corresponds tothe peripheral speed of the rotating screen drum.

In this process, the formation of the small doped domes takes place bythe following mechanism:

The pressure of the nozzle coating bar conveys the doped compositionthrough the screen perforation onto the backing material. The size ofthe domes formed is determined in advance by the diameter of the screenperforation. The screen is lifted from the backing in accordance withthe rate of transportation of the backing web (rotary speed of thescreen drum). As a consequence of the high adhesion of the self-adhesivecomposition and of the internal cohesion of the hotmelt, the limitedsupply of hotmelt self-adhesive composition in the perforations is drawnin sharp definition from the base of the domes, that is already adheringto the backing, and is conveyed onto the backing by the pressure of thecoating bar.

Following the end of this transportation, the more or less highly curvedsurface of the dome forms over the predefined base area depending on therheology of the hotmelt self-adhesive composition. The height-to-baseratio of the dome depends on the ratio of the perforation diameter tothe wall thickness of the screen drum and on the physical properties(flow behaviour, surface tension and contact angle on the backingmaterial) of the self-adhesive composition.

For the screen in thermal screen printing, the web-to-hole ratio can beless than 3:1, preferably less than or equal to 1:1 and, in particular,equal to 1:3.

The above-described mechanism of formation of the domes requires,preferentially, backing materials that are absorbent or at leastwettable by the doped composition. Non-wetting backing surfaces must bepretreated by chemical or physical methods. This can be done by means ofadditional measures such as corona discharge, for example, or by coatingwith wetting agents.

Using the printing technique indicated it is possible to lay down thesize and shape of the domes in a defined manner. The bond strengthvalues which are relevant for use, which determine the quality of theproducts formed, are within very narrow tolerances provided that coatingis carried out correctly. The base diameter of the domes can be chosento be from 10 to 5000 μm, the height of the domes is from 20 to 2000 μm,preferably from 50 to 1000 μm, the low-diameter range being intended forsmooth backings and the range of greater diameter and greater domeheight being intended for rough or highly porous backing materials.

The positioning of the domes on the backing is laid down in a definedmanner by the geometry of the applicator unit, for example the gravureor screen geometry, which can be varied within wide limits. With the aidof the parameters indicated it is possible, by way of adjustablevariables, to establish with very great precision the desired profile ofproperties of the coating, harmonized with the various backing materialsand applications.

The backing material is preferably coated at a rate of more than 2m/min, preferably from 20 to 220 m/min, the chosen coating temperaturebeing greater than the softening point.

The doped device can be applied to the backing material with a weightper unit area of greater than 15 g/m², preferably between 90 and 400g/m² and, with very particular preference, between 130 and 300 g/m².

The percentage area that is coated with the doped device should be atleast 20% and can range up to approximately 95%, for specific productspreferably from 40 to 60% and from 70 to 95%. This can be achieved, ifdesired, by means of multiple application, with the possible use ifdesired of devices having different properties and dopes.

The combination of the doped devices and of the partial coating firstlyensures secure bonding of the medical product to the skin and secondlyprevents at least visually discernible allergic or mechanical skinirritations, even in the case of an application which extends overseveral days.

The epilation of corresponding body regions and the transfer ofcomposition to the skin are negligible owing to the high cohesiveness ofthe device, since the device is not anchored to skin and hair—rather,the anchorage of the device to the backing material, at up to 12 N/cm(sample width), is good for medical applications.

Because of the intended breakage points that have been formed in thecoating, layers of skin are no longer displaced with one another oragainst one another in the course of detachment. The non-displacement ofthe layers of skin and the relatively low level of epilation lead to anunprecedented degree of painlessness in such strongly adhering systems.In addition, the individual biomechanical control, which results in ademonstrable reduction in the bond strength of this device, assistsdetachability.

Depending on the backing material and its temperature sensitivity,composition can be applied directly or can be applied first to anauxiliary support and then transferred to the ultimate backing.

Subsequent calendering of the coated product and/or pretreatment of thebacking, such as corona irradiation, for better anchorage of theadhesive layer, may also be advantageous.

In addition, treating the composition by electron beam post-crosslinkingor by UV irradiation can lead to an improvement in the desiredproperties.

Suitable backing materials are all rigid and elastic sheetlikestructures of synthetic and natural raw materials. Preference is givento backing materials which, following the application of the adhesivecomposition, can be employed in such a way that they fulfil thecharacteristics of a functional dressing.

Examples are textiles such as wovens, knits, lays, nonwovens, laminates,nets, films, foams and papers. In addition, these materials can bepretreated or aftertreated. Common pretreatments are corona andhydrophobicization; customary aftertreatments are calendering, thermalconditioning, laminating, punching and covering.

The backing material coated with the composition can have an airpermeability of greater than 1 cm³/(cm^(2*)s), preferably greater than15 cm³/(cm^(2*)s) and, with very particular preference, greater than 70cm³/(cm^(2*)s), and a water vapour permeability of greater than 500g/(m^(2*)24 h), preferably greater than 1000 g/(m^(2*)24 h) and, withvery particular preference, greater than 2000 g/(m^(2*)24 h).

Finally, following the coating operation, the device can be covered withan anti-adhesive backing material, such as siliconized paper, orprovided with a wound pad or with padding.

Subsequently, the device is punched out in the desired size.

It is particularly advantageous if the device is sterilized, preferablyby means of γ (gamma) radiation. This is particularly suitable forsubsequent sterilization of a block copolymer-based polymer systemcontaining no double bonds. This applies in particular to thestyrene-propylene-ethylene-styrene block copolymer of the invention. Inthis case the properties are not subject to any changes that aresignificant for the application.

The device of the invention can have a bond strength of at least 1.5N/cm, in particular a bond strength of between 2.5 and 5 N/cm. Higherbond strengths may be achieved on other substrates.

The intention in the text below is to describe particularly advantageousembodiments of the invention, without wishing thereby unnecessarily torestrict the invention.

In accordance with the invention, example formulations for releasingvarious active substances were prepared. All formulations were preparedwithout solvent in a laboratory kneading apparatus at a temperature ofbetween 90° C. and 180° C. The pharmaceutical active substance was addedduring the cooling phase at a temperature which in the case of solidpharmaceuticals was approximately 10° C. above the respective meltingpoint. The production of laboratory samples for testing the formulationswas carried out with the aid of a hot press.

EXAMPLE 1 5% by Weight Active Substance Preparation

39.0 g of Septon 4033 (Kuraray), 57.0 g of Regalite 91 (Hercules), 46.5g of Hercules MBG 274 (Hercules) and 1.4 g of Irganox 1010 (Ciba) weremelted in a laboratory kneading apparatus at 150° C. and homogenizedover a period of approximately 90 minutes. Subsequently, at 100° C., 7.5g of ibuprofen were added and the mixture was homogenized for a further60 minutes. The hot mass was subsequently poured into a siliconized pan.

To produce laboratory samples, 10.0 g of the cooled mass were pressed ina melt press at 100° C. between two siliconized release paper sheets toa layer thickness of 400 μm. Subsequently, following removal of therelease paper, one side of the adhesive layer was laminated withsiliconized polyester film. On the opposite side, an adhesive polyesterfilm was laminated. The specimens for determining the bond strength andthe release of active substance were prepared from this sample.

The result was a colourless, transparent sample having excellent bondstrength and very good cohesion. The bond strength, measured on PMMA(polymethyl methacrylate) in the 90° peel test, was 18.7 N/cm at a peelrate of 300 mm/min.

The release of active substance was determined by means of aKeshary-Chien cell using a silicone membrane and an aqueous phosphatebuffer as receptor phase. Over a period of 24 h, 281 μg/cm² of theincorporated active substance were released.

EXAMPLES 2 to 6 5% by Weight Active Substance Preparation

The following example formulations were prepared following the procedureof Example 1.

Example Active substance Added at 2 salicylic acid 160° C. 3 diclofenac160° C. 4 benzocaine 100° C. 5 licocaine *HCl 130° C. 6 bufexamac 160°C.

EXAMPLES 7 to 9 1% by Weight Active Substance Preparation

40.7 g of Septon 4033 (Kuraray), 59.4 g of Regalite 91 (Hercules), 48.4g of Hercules MBG 274 (Hercules) and 1.4 g of Irganox 1010 (Ciba) weremelted in a laboratory kneading apparatus at 150° C. and homogenizedover a period of approximately 90 minutes. Subsequently, at thetemperature indicated in the table, 1.5 g of the respective activesubstance were added and the mixture wasp homogenized for a further 60minutes. Subsequent processing followed the procedure described underExample 1.

Example Active substance Added at 7 clotrimazole 150° C. 8 econazole100° C. 9 diphenhydramine *HCl 170° C.

EXAMPLES 10 1% By Weight Active Substance Preparation

In accordance with the invention, an unfoamed substance release devicewas produced which contained a non-hyperaemic active substance. Theactive substance used was ibuprofen.

The backing material consisted of a nonelastic cotton fabric having amaximum tensile strength of more than 80 N/cm and an extension atmaximum tensile strength of less than 20%.

The composition of this hotmelt pressure-sensitive adhesive compositionwas as follows:

an SEPS block copolymer consisting of hard and soft segments, with astyrene content in the polymer of 13 mol %; its proportion in theadhesive composition is 35% by weight (Kuraray Co.)

a paraffinic hydrocarbon resin whose proportion in the adhesivecomposition is 63% by weight

an anti-ageing agent with a proportion of less than 1.0% by weight(Irganox 1010 Ciba)

ibuprofen with a proportion of 1%.

The components of the adhesive that were employed were homogenized in athermal mixer at 165° C. for 1.5 hours. The active substance was addedin the cooling phase, at 100° C., and homogenization was continued inthe mixer for 75 minutes.

The self-adhesive composition was applied with a nozzle over the wholearea of the backing. The direct coating operation took place at 50 m/minand at a temperature of 120° C. The backing material was coated with 170g/m².

The plaster material produced in this way shows a comparably goodrelease of the active substance (liberation study).

Following application, no skin irritations were found.

What is claimed is:
 1. A substance release device comprising at least 3%by weight of a styrene-ethylene-propylene-styrene (“SEPS”) blockcopolymer, additional polymers based on block copolymers having at leastone hard phase (A) based on styrene or derivatives thereof and at leastone soft phase (B) selected from the group consisting of ethylene,butylenes, propylene, isoprene, butadiene and mixtures thereofconstructed on the basis of diblock (A-B) and/or triblock (ABA) havingless than 80% by weight diblock copolymers and at least one locally orsystemically active substance which does not have a hyperaemic actionand is selected from the group consisting of antimycotics, antiseptics,nonsteroidal antiheumatics, antipuritics, local anaesthetics,antipsonatics and keratolytics wherein the copolymer is foamed and has aglass transition temperature of less than 15° C. at a frequency of 0.1rad/s and is in the form of an adhesive composition and the active isdispersed in the device.
 2. Substance release device according to claim1 wherein the device comprises different active substances.
 3. Substancerelease device according to claim 1 wherein the device comprises from0.01 to 60% by weight active substance or substances.
 4. Substancerelease device according to claim 1 wherein the overall styrene contentin the polymer system is less than 35% by weight.
 5. Substance releasedevice according to claim 1 wherein the device is a hotmelt adhesivecomposition having an SEPS block copolymer proportion of at least 3% byweight and consisting of a) from 3 to 90% by weight of block copolymers,b) from 5 to 80% by weight of tackifiers, c) less than 60% by weight ofplasticizers, d) less than 15% by weight of additives, e) less than 5%by weight of stabilizers, f) less than 20% by weight of active substancerelease auxiliaries, and g) less than 20% by weight of active substanceor substances.
 6. Substance release device according to claim 1 whereinthe device is applied partially to a backing material by means selectedfrom the group consisting of halftone printing, thermal screen printing,thermal flexographic printing and intaglio printing.
 7. Substancerelease device according to claim 1 wherein the device is applied to abacking material by spraying.
 8. Substance release device according toclaim 1 wherein the device is applied in the form of polygeometric domesto the backing material.
 9. Substance release device according to claim1 wherein the device is applied to a backing material with a weight perunit area of greater than 15 g/m².
 10. Substance release deviceaccording to claim 1 wherein the percentage area on a backing materialthat is coated with the device is at least 20%.
 11. Substance releasedevice according to claim 1 wherein a backing material coated with thedevice has an air permeability of greater than 1 cm³/(cm²*s). 12.Substance release device according to claim 1 wherein the device issterilized by means of γ (gamma) radiation.
 13. Substance release deviceaccording to claim 1 wherein the device has a bond strength of at least1.5 N/cm.
 14. Substance release device of claim 1 wherein the SEPS blockcopolymer comprises polystyrene blocks (“S”) and blocks of hydrogenatedpolyisoprene (“EP”) or hydrogenated poly(butadiene-co-isoprene) (“EEPP”)and has an S/EP or S/EEP diblock fraction of more than 30%. 15.Substance release device according to claim 1 comprising 0.1% to 20% byweight active substance or substances.
 16. Substance release deviceaccording to claim 4 wherein the overall styrene content is between 5%and 30% by weight.
 17. Substance release device according to claim 5wherein the tackifiers are selected from the group consisting ofaliphatic hydrocarbon resins, hydrogenated terpene resins, hydrogenatedhydrocarbon resins, cyclopentadiend resins and low molecular masspolyisobutylenes.
 18. Substance release device according to claim 5wherein the plasticizers are selected from the group consisting ofparaffin oils, aliphatic hydrocarbon oils, waxes and fatty acetates andalcoholates.
 19. Substance release device according to claim 1 whereinthe dynamic glass transition temperature of the elastomer phase isbetween −3° C. and −30° C.
 20. Substance release device according toclaim 1 wherein the dynamic glass transition temperature of theelastomer phase is between −9° C. and −25° C.
 21. Substance releasedevice according to claim 9 wherein the backing material has a weightper unit area between 90 g/m² and400 g/m².
 22. Substance release deviceaccording to claim 9 wherein the backing material has a weight per unitarea between 130 g/m² and 300 g/m².
 23. Substance release deviceaccording to claim 10 wherein the percentage area of the backingmaterial coated with the device is between 40% and 60%.
 24. Substancerelease device according to claim 10 wherein the percentage area of thebacking material coated with the device is between 70% and 95%. 25.Substance release device according to claim 13 wherein the bond strengthis between 2.5 N/cm and 5 N/cm.